Chiral quaternary nitrogen guanidinium salts derived from amino acids, processes for their preparation and uses thereof

Abstract

The application belongs to the field of catalysts, and particularly relates to a chiral quaternary nitrogen guanidine salt derived from an amino acid, a preparation method thereof and application thereof. The application provides a compound shown in formula I and a preparation method thereof. The compound has good catalytic performance in asymmetric alkylation reaction and / or arylization reaction. Experiments show that the catalytic performance of the compound in asymmetric arylization reaction participated by benzene alkyne is superior to that of existing chiral quaternary ammonium salt catalysts or chiral quaternary phosphonium salt catalysts. Therefore, the application has good application prospect.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of catalysts, and particularly relates to a chiral quaternary nitrogen guanidinium salt derived from an amino acid, a preparation method thereof and use thereof. BACKGROUND

[0002] Phase transfer catalysts are widely used in the construction of chiral centers, the catalytic synthesis of natural products and drug molecules due to their structural modification, simple experimental operation and mild reaction conditions. The most studied phase transfer catalyst is quaternary ammonium salt (R4N + X - ), but most of the NR4 + It is easy to decompose and deactivate under strong alkaline conditions, thus limiting its application in industry to some extent [(a) Hughes, D.; Dolling, U.; Ryan, K.; Schoenewaldt, E.; Grabowski, E. J. Org. Chem. 1987, 52, 4745-4752; (b) Gratzer, K.; Waser, M. Synthesis 2012, 44, 3661-3670.].

[0003]

[0004] Chiral amino acids, as an inexpensive and readily available source of chirality, have been used to synthesize a variety of chiral catalysts (Liu, X. H.; Dong, S. X.; Lin, L. L.; Feng, X. M. Chin. J. Chem. 2018, 36, 791-797.), and have achieved efficient chiral induction in various types of reactions. Therefore, based on inexpensive and readily available chiral amino acid raw materials and guanidinium salt structures with higher stability sp 2 hybrid nitrogen centers (Patel, N., Sood, R. & Bharatam, P. V. Chem. Rev. 2018, 118, 8770-8785), a chiral quaternary nitrogen guanidinium salt catalyst was designed and synthesized. Compared with the traditional quaternary ammonium salt (R4N + X — ) phase transfer catalyst, the compound has the advantages of enhanced stability, simple synthesis method, easy modification and rich structural changes. At the same time, the catalytic activity and enantioselectivity of the current efficient phase transfer catalyst in many asymmetric reactions are not ideal. Therefore, it is still necessary to develop new efficient phase transfer catalysts to be suitable for more types of catalytic reactions. SUMMARY

[0005] In view of the problems of the prior art, the purpose of the present application is to provide a chiral quaternary nitrogen guanidinium salt derived from an amino acid, a preparation method thereof and use thereof.

[0006] a compound of formula I, or a stereoisomer thereof, or a salt thereof:

[0007]

[0008] wherein R 1 , R 2 are each independently selected from the group consisting of: hydrogen, hydroxyl, halogen, carboxyl, substituted or unsubstituted C1-C 11 carbonyl, substituted or unsubstituted C1-C 11 ester, substituted or unsubstituted C1-C 11 alkenyl, substituted or unsubstituted C1-C 11 alkynyl, substituted or unsubstituted C1-C 11 alkyl, substituted or unsubstituted C1-C 11 alkoxy, substituted or unsubstituted benzyl, substituted or unsubstituted benzyloxy, polysubstituted siloxy, wherein the substituents are selected from the group consisting of C1-C 11 alkyl, C3-C 10 cycloalkyl, C6-C 10 aryl, halogen-substituted C6-C 10 aryl, cyano, hydroxyl, carboxyl, or halogen;

[0009] or, R 1 and R 2 are connected to form a substituted or unsubstituted C6-C 10 aryl, substituted or unsubstituted C5-C 10 cycloalkyl, wherein the substituents are selected from the group consisting of C1-C 11 alkyl, C6-C 10 aryl, cyano, hydroxyl, carboxyl, or halogen;

[0010] R 3 is selected from the group consisting of: hydrogen, substituted or unsubstituted C1-C 13 alkyl, substituted or unsubstituted C1-C 13 alkynyl, substituted or unsubstituted benzyl, wherein the substituents are selected from the group consisting of C1-C 11 alkyl, C6-C 10 aryl, cyano, hydroxyl, carboxyl, or halogen;

[0011] R 4 is selected from the group consisting of: hydrogen, hydroxyl, substituted or unsubstituted C1-C 10 primary amine, substituted or unsubstituted C1-C 10 alkoxy, substituted or unsubstituted C1-C 21alkyl, substituted or unsubstituted phenoxy, substituted or unsubstituted anilino, substituted or unsubstituted benzyloxy, substituted or unsubstituted benzylamino, substituted or unsubstituted 1-naphthoxy, substituted or unsubstituted 1-naphthylamino, substituted or unsubstituted 2-naphthoxy, substituted or unsubstituted 2-naphthylamino, wherein the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, C6-C10 aryl, C1-C2 haloalkyl, C1-C2 haloalkoxy, C1-C2 alkoxy, cyano, hydroxy, carboxy, halogen, amino, nitro, and combinations thereof; 11 alkyl, C3-C6 cycloalkyl, C6-C10 aryl, C1-C2 haloalkyl, C1-C2 haloalkoxy, C1-C2 alkoxy, cyano, hydroxy, carboxy, halogen, amino, nitro, and combinations thereof; 10 alkyl, C3-C6 cycloalkyl, C6-C10 aryl, C1-C2 haloalkyl, C1-C2 haloalkoxy, C1-C2 alkoxy, cyano, hydroxy, carboxy, halogen, amino, nitro, and combinations thereof; 11 alkyl, C3-C6 cycloalkyl, C6-C10 aryl, C1-C2 haloalkyl, C1-C2 haloalkoxy, C1-C2 alkoxy, cyano, hydroxy, carboxy, halogen, amino, nitro, and combinations thereof; 10 alkyl, C3-C6 cycloalkyl, C6-C10 aryl, C1-C2 haloalkyl, C1-C2 haloalkoxy, C1-C2 alkoxy, cyano, hydroxy, carboxy, halogen, amino, nitro, and combinations thereof;

[0012] R a alkyl, C3-C6 cycloalkyl, C6-C10 aryl, C1-C2 haloalkyl, C1-C2 haloalkoxy, C1-C2 alkoxy, cyano, hydroxy, carboxy, halogen, amino, nitro, and combinations thereof; 10 alkyl, C3-C6 cycloalkyl, C6-C10 aryl, C1-C2 haloalkyl, C1-C2 haloalkoxy, C1-C2 alkoxy, cyano, hydroxy, carboxy, halogen, amino, nitro, and combinations thereof; 11 alkyl, C3-C6 cycloalkyl, C6-C10 aryl, C1-C2 haloalkyl, C1-C2 haloalkoxy, C1-C2 alkoxy, cyano, hydroxy, carboxy, halogen, amino, nitro, and combinations thereof;

[0013] R 5 , R 6 , R 7 , R 8 each independently selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, C6-C10 aryl, C1-C2 haloalkyl, C1-C2 haloalkoxy, C1-C2 alkoxy, cyano, hydroxy, carboxy, halogen, amino, nitro, and combinations thereof;

[0014] or, R 5 and R 6 are linked to form a 5- to 7-membered heterocyclic ring;

[0015] or, R 7 and R 8 are linked to form a 5- to 7-membered heterocyclic ring;

[0016] or, R 6 and R 7 are linked to form a 5- to 7-membered heterocyclic ring;

[0017] n is selected from 0, 1;

[0018] X - is an anion.

[0019] Preferably, the compound has a structure according to Formula I-a or I-b:

[0020]

[0021] Preferably, R 1 is selected from the group consisting of hydrogen, hydroxy, halogen, substituted or unsubstituted benzyloxy, substituted or unsubstituted C2 ester group, substituted or unsubstituted C1-C2 alkoxy, polysubstituted siloxy, wherein the substituents are selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, C6-C10 aryl, C1-C2 haloalkyl, C1-C2 haloalkoxy, C1-C2 alkoxy, cyano, hydroxy, carboxy, halogen, amino, nitro, and combinations thereof; 10 alkyl, C3-C6 cycloalkyl, C6-C10 aryl, C1-C2 haloalkyl, C1-C2 haloalkoxy, C1-C2 alkoxy, cyano, hydroxy, carboxy, halogen, amino, nitro, and combinations thereof; 10 alkyl, C3-C6 cycloalkyl, C6-C10 aryl, C1-C2 haloalkyl, C1-C2 haloalkoxy, C1-C2 alkoxy, cyano, hydroxy, carboxy, halogen, amino, nitro, and combinations thereof; 10 alkyl, C3-C6 cycloalkyl, C6-C10 aryl, C1-C2 haloalkyl, C1-C2 haloalkoxy, C1-C2 alkoxy, cyano, hydroxy, carboxy, halogen, amino, nitro, and combinations thereof;10 Aryl, halogen;

[0022] R 2 Selected from hydrogen;

[0023] Or, R 1 With R 2 They can be linked together to form phenyl, cyclopentane, or cyclohexane;

[0024] R 3 Selected from hydrogen.

[0025] Preferred, R 4 Selected from: hydroxyl, substituted or unsubstituted C1-C2 alkylamine, substituted or unsubstituted C1 alkoxy, substituted or unsubstituted aniline, wherein the substituent is selected from halogen, C1-C4 alkyl, C6 ... 10 aryl, methyl-substituted phenyl, amino

[0026] R a It is selected from C1 to C6 alkyl groups, substituted or unsubstituted phenyl groups, wherein the substituents are selected from C1 to C4 alkyl groups or halogens.

[0027] Preferred, R 5 R 6 R 7 R 8 They are C1 to C4 alkyl groups, respectively.

[0028] Or, R 5 With R 6 Connected into 5- to 7-membered heterocyclic rings;

[0029] Or, R 7 With R 8 Connected into 5- to 7-membered heterocyclic rings;

[0030] Or, R 6 With R 7 They connect to form 5- to 7-membered heterocyclic rings.

[0031] Preferably, X is selected from: chloride ion, bromide ion, iodide ion, trifluoromethanesulfonate ion, borate ion or phosphate ion.

[0032] Preferably, the compound has the structural formula shown in Formula Ic:

[0033]

[0034] in,

[0035] R b The substituent is independently selected from halogens, C1-C4 alkyl groups, substituted or unsubstituted phenyl groups; wherein the substituent is selected from halogens, fluorinated C1-C4 alkyl groups, C1-C4 alkyl groups, C6-C6 alkyl groups, and C6-C4 alkyl groups.10 Aryl;

[0036] R c1 R c2 Each C6 to C6 is independently selected from substituted or unsubstituted C6 to C6. 10 aryl; wherein the substituents are selected from halogens, C1-C4 alkyl groups, C6-C4 alkyl groups, and C6-C4 alkyl groups. 10 Aryl;

[0037] i and j are independently chosen from 1, 2, or 3; k is chosen from 1 or 2.

[0038] Preferably, the structural formula of the compound is selected from one of the following structures:

[0039]

[0040]

[0041] The present invention also provides a method for preparing the above-mentioned compound, comprising the following steps:

[0042]

[0043] Step 1: React compound I-1 with an alcohol or amine to obtain compound I-2;

[0044] When R 1 When R is hydroxyl, proceed to steps 2 and 3. 1 If it is not a hydroxyl group, proceed to step 3;

[0045]

[0046] Step 2, mix compound I-2 with R 9 -LG reaction yields compound I-2′;

[0047] Among them, R 9 Selected from hydrogen, substituted or unsubstituted C1 to C2. 11 Alkyl, substituted or unsubstituted benzyl, substituted or unsubstituted 1-methylnaphthalene, substituted or unsubstituted 2-methylnaphthalene, substituted or unsubstituted 9-methylanthracene, polysubstituted silyl, substituted or unsubstituted C1-C 11 Acyl group; substituents selected from C1 to C2. 11 Alkyl, C6-C 10 Aryl, cyano, carboxyl, halogen, amino; LG is selected from Cl, Br, I, OTf;

[0048]

[0049] Step 3: React compound I-2 or compound I-2′ with trifluoroacetic acid to obtain compound I-3;

[0050]

[0051] Step 4, reacting compound I-3 with imidazoline chloride salt to obtain compound I-4;

[0052]

[0053] Step 5, reacting compound I-4 with metal salt to obtain compound of formula I.

[0054] Preferably, in step 1, the reaction is carried out in solvent dichloromethane or tetrahydrofuran, the alcohol or amine in the reactants is selected from one of primary amine, secondary amine, primary alcohol, secondary alcohol, the reaction temperature is 20-50℃, and the reaction time is 4-24h;

[0055] and / or, in step 2, the reaction is carried out in solvent tetrahydrofuran, the reaction is carried out under the action of base selected from at least one of sodium hydride, triethylamine or imidazole, the reaction temperature is 0-25℃, and the reaction time is 5-24h;

[0056] and / or, in step 3, the reaction is carried out in solvent dichloromethane, the reaction temperature is 0-25℃, and the reaction time is 1-2h;

[0057] and / or, in step 4, the reaction is carried out in solvent acetonitrile, the reaction is carried out under the action of base selected from triethylamine, the reaction temperature is 25-80℃, and the reaction time is 10-24h;

[0058] and / or, in step 5, the reaction is carried out in solvent dichloromethane or tetrahydrofuran, the reaction temperature is 20-35℃, and the reaction time is 4-10h.

[0059] The application also provides the use of the above-mentioned compound, or a stereoisomer thereof, or a salt thereof as a phase transfer catalyst for catalyzing asymmetric alkylation reaction and / or arylization reaction.

[0060] The compounds and derivatives provided in the application can be named according to the IUPAC (International Union of Pure and Applied Chemistry) or CAS (Chemical Abstract Service, Columbus, OH) nomenclature system.

[0061] Definitions of terms used in the application: unless otherwise specified, the initial definition of a group or term provided herein applies throughout the specification for that group or term; for terms not specifically defined herein, the meaning given to them by one of ordinary skill in the art in light of the disclosure and context should be given to them.

[0062] “Substitution” refers to the replacement of a hydrogen atom in a molecule by another different atom or molecule.

[0063] The minimum and maximum number of carbon atoms in a hydrocarbon group is indicated by a prefix, e.g., the prefix C a -C b Alkyl indicates any alkyl group of from "a" to "b" carbon atoms. Thus, for example, "C1-C4 alkyl" refers to an alkyl group containing from 1 to 4 carbon atoms.

[0064] "Alkyl" refers to a saturated hydrocarbon chain having the specified number of members. For example, C1-C6 alkyl refers to an alkyl group having from 1 to 6 members, e.g., from 1 to 4 members. The alkyl group can be straight or branched. Representative branched alkyl groups have one, two, or three branches. The alkyl group can be optionally substituted with one or more substituents as defined herein. Alkyl includes methyl, ethyl, propyl (n-propyl and isopropyl), butyl (n-butyl, isobutyl, and t-butyl), pentyl (n-pentyl, isopentyl, and neopentyl), and hexyl. The alkyl group can also be part of other groups, e.g., C1-C6 alkoxy.

[0065] "Cycloalkyl" refers to a saturated or partially saturated cyclic group having from 3 to 14 carbon atoms and no ring heteroatoms and having a single ring or multiple rings (including fused, bridged, and spiro ring systems). For multiple ring systems having both aromatic and non-aromatic rings free of ring heteroatoms, the term "cycloalkyl" applies when the point of attachment is to a non-aromatic carbon atom (e.g., 5,6,7,8,- tetrahydronaphthalen-5-yl). The term "cycloalkyl" includes cycloalkenyl groups, such as cyclohexenyl. Examples of cycloalkyl groups include, for example, adamantyl, cyclopropyl, cyclobutyl, cyclohexyl, cyclopentyl, cyclooctyl, cyclopentenyl, and cyclohexenyl.

[0066] "Alkenyl" refers to a straight or branched hydrocarbon group having from 2 to 10 carbon atoms and in some embodiments from 2 to 6 carbon atoms or from 2 to 4 carbon atoms and having at least 1 site of vinyl unsaturation (>C=C<). For example, C2-C6 alkenyl is intended to include both double and triple bond alternatives. C2-C6 alkenyl thus includes ethenyl, propenyl, isopropenyl, 1,3- butadienyl, etc. a -C b Alkenyl refers to an alkenyl group having a to b carbon atoms and is intended to include, for example, ethenyl, propenyl, isopropenyl, 1,3-butadienyl, and the like.

[0067] "Akynyl" refers to a straight-chain or branched-chain monovalent hydrocarbon group containing at least one triple bond. The term "akynyl" is also intended to include those hydrocarbon groups having one triple bond and one double bond. For example, C2-C6 akynyl is intended to include ethynyl, propynyl, and the like.

[0068] "Halogen" is fluorine, chlorine, bromine, or iodine.

[0069] "Heterocycle," "heterocycloalkyl" refers to a saturated or unsaturated ring that is non-aromatic; containing at least one heteroatom; wherein a heteroatom refers to a nitrogen atom, an oxygen atom, a sulfur atom;

[0070] "Heteroaryl" means an aromatic unsaturated ring group containing at least one heteroatom; wherein the heteroatom means nitrogen atom, oxygen atom, sulfur atom;

[0071] "R a and R b are connected to form a heterocyclic ring" means that at least one atom in R a and R b is connected by a chemical bond, so that the atom or atom chain connected by R a and R b together as part of the skeleton of the ring structure and R a and R b together constitute a heterocyclic ring.

[0072] "Stereoisomer" includes enantiomers and diastereomers.

[0073] The present application is based on cheap and readily available chiral amino acid raw materials and guanidine salt structure with higher stability sp 2 hybrid nitrogen center, and a chiral quaternary nitrogen guanidine salt catalyst is designed and synthesized. Compared with the traditional quaternary ammonium salt (R4N + X — phase transfer catalyst, the compound has the advantages of enhanced stability, simple synthesis method, easy modification and rich structure variation, and also shows high catalytic effect in the asymmetric arylation reaction of phenylacetylene.

[0074] Obviously, according to the above content of the present application, according to the ordinary technical knowledge and common means in the art, other various forms of modification, replacement or change can be made without departing from the above basic technical idea of the present application.

[0075] The above content of the present application will be further described in detail through the specific embodiments in the form of examples. However, this should not be understood as limiting the scope of the above subject matter of the present application to the following examples. Any technology realized based on the above content of the present application belongs to the scope of the present application. DETAILED DESCRIPTION

[0076] In the following examples and experimental examples, the reagents and raw materials not specifically described are commercially available.

[0077] Example 1: Synthesis of amide compound I-2-1

[0078]

[0079] In a round bottom flask, add magnetic stirrer, Boc-protected amino acid (1.0 equiv.), dichloromethane (0.5 M) or tetrahydrofuran (0.5 M) as solvent. Cool to 0 °C, slowly add triethylamine (1.2 equiv.) at this temperature, then slowly drop isobutyl chloroformate (1.2 equiv.), after 30 minutes of reaction at room temperature, cool to 0 °C again. Add primary or secondary amine (1.2-1.5 equiv.) at this temperature, react at 20-50 °C for 4-24 hours. After the reaction is completed, add dichloromethane (0.5 M) or ethyl acetate (0.5 M) to dilute the reaction system, wash with saturated potassium bisulfate, saturated sodium bicarbonate, saturated sodium chloride in turn once. Dry the organic phase with anhydrous sodium sulfate, filter, concentrate under reduced pressure, and directly proceed to the next step.

[0080] Example 2: Synthesis of ester compound I-2-2

[0081]

[0082] In a round bottom flask, add magnetic stirrer, Boc-protected amino acid (1.0 equiv.), dichloromethane (0.5 M) as solvent. Cool to 0 °C, slowly add dichlorosulfoxide (1.5 equiv.) at this temperature, add substituted alcohol (1.5-15.0 equiv.) after 30 minutes of reaction, then restore room temperature for 3-5 hours of reaction. After the reaction is completed, spin dry the solvent to obtain the crude product, and directly proceed to the next step.

[0083] Example 3: Synthesis of amide compound I-2' (R 1 = OH)

[0084]

[0085] In a round bottom flask, add magnetic stirrer, Boc-protected amide I-2 (1.0 equiv.), tetrahydrofuran (0.4 M) as solvent. Cool to 0 °C, add NaH (2.5 equiv., 60% dispersion in mineral oil), triethylamine (2.5 equiv.) or imidazole (2.5 equiv.) in batches, after 30 minutes of reaction, slowly drop R 9 -LG (1.5-2.5 equiv.), then raise the reaction system to room temperature for reaction until the amide substrate I-2 is completely consumed (5-24 h). After the reaction is completed, cool the reaction system to 0 °C, add ice water and aq. KHSO4 or HCl (2.0 M) to quench the reaction, extract with ethyl acetate (3x50 mL), combine the organic phases. Wash the organic phase with saturated sodium chloride solution, dry with anhydrous sodium sulfate, filter, concentrate under reduced pressure, and separate by column chromatography (eluent: petroleum ether: ethyl acetate = 4:1-3:1) to obtain the target product I-2'.

[0086] Example 4: Synthesis of amide compound I-3

[0087]

[0088] Into a round bottom flask was placed I-2 from either Example 2 or Example 3, a magnetic stir bar, and dichloromethane (1.0 M) as solvent. The reaction mixture was cooled to 0 °C and trifluoroacetic acid (1.0 mL / mmol) was added slowly at this temperature. After 1 hour at room temperature, the reaction was monitored by TLC. When the starting material I-2 was consumed, the reaction mixture was cooled to 0 °C, diluted with dichloromethane (0.5 M), and the pH was adjusted to 11-12 by the slow addition of 50% aq. NaOH. The organic phase was separated and the aqueous phase was extracted with dichloromethane. The combined organic phases were washed with saturated NaCl solution, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether: ethyl acetate = 4:1 to 0:1) to give the desired product I-3.

[0089] Example 5: Synthesis of quaternary nitrogen chlorinated guanidine salt I-4

[0090]

[0091] Into a 25 mL round bottom flask was placed a magnetic stir bar, compound I-3 (1.0 equiv.), acetonitrile (1.0 M) as solvent, and triethylamine (2.5 equiv.) and freshly prepared imidazoline chlorinated salt (1.5 equiv.) was added slowly with stirring. The reaction was refluxed at 25-80 °C. After the reaction was completed, 2 M HCl was added to quench the reaction, and the mixture was extracted with dichloromethane. The combined organic phases were washed with saturated NaCl solution, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: ethyl acetate: methanol = 10:1 to 6:1) to give the desired product I-4.

[0092] Example 6: Synthesis of quaternary nitrogen guanidine salt I

[0093]

[0094] Into a 10 mL catalytic test tube was placed a magnetic stir bar, compound I-4 (1.0 equiv.), MX (1.1-10.0 equiv.), dichloromethane (0.2 M) or tetrahydrofuran (0.2 M) as solvent, and the reaction was carried out at 20-35 °C for 4-10 hours. The reaction mixture was filtered through celite, and the filter cake was washed with dichloromethane. The solvent was removed by rotary evaporation to give the product IA-IAL.

[0095] It should be noted that in the above reaction schemes of Examples 1-6, the specific structure of each substituent is determined according to the structure of the corresponding group of compounds IA-IAL.

[0096] Example 7: Synthesis of quaternary nitrogen guanidine salt IA

[0097] The procedure is similar to that described in Example 1 and 4-6, with the replacement of the starting materials according to the corresponding substituents in the product.

[0098]

[0099] Yellow solid, mp 211-212 °C; overall yield 78%; [a] 20 D = + 139.2 (c = 0.556 g / 100 mL, λ = 589 nm, in CH2CI2); 1 H NMR (400 MHz, Chloroform-d) δ 8.79 (d, J = 9.2 Hz, 1H), 7.59-7.57 (m, 2H), 7.41-7.39 (m, 2H), 7.30-7.24 (m, 4H), 7.20-7.15 (m, 2H), 6.18 (d, J = 9.2 Hz, 1H), 5.22 (dd, J = 6.4, 4.4 Hz, 1H), 3.71-3.08 (m, 9H), 2.18-1.57 (m, 14H). 13 C{ 1 H} NMR (101 MHz, Chloroform-d) δ 171.0, 157.9, 141.7, 128.7, 128.7, 128.2, 127.4, 127.2, 59.5, 57.7, 49.0, 30.6, 25.2, 21.1. HRMS (ESI) calcd for C 28 H 37 N4O + ([M-I - ]) + = 445.2962, Found 445.2962.

[0100] Example 8: Synthesis of quaternary guanidinium salt IB

[0101] The procedure is similar to that described in Example 1 and 4-6, with the replacement of the starting materials according to the corresponding substituents in the product.

[0102]

[0103] White solid, mp 240-241 °C; overall yield 57%; [a] 22 D = + 141.9 (c = 0.955 g / 100 mL, λ = 589 nm, in CH2CI2); 1H NMR (400 MHz, Chloroform-d) δ 8.56 (d, J = 9.2 Hz, 1H), 7.55 - 7.53 (m, 2H), 7.46 - 7.44 (m, 2H), 7.29 - 7.26 (m, 4H), 7.21 - 7.16 (m, 2H), 6.22 (d, J = 9.2 Hz, 1H), 5.53 - 5.49 (m, 1H), 4.28 - 4.22 (m, 1H), 3.60 - 3.54 (m, 4H), 3.40 - 3.32 (m, 4H), 2.94 - 2.90 (m, 1H), 2.86 - 2.78 (m, 1H), 2.16 - 2.01 (m, 2H), 1.97 - 1.86 (m, 5H), 1.80 - 1.54 (m, 8H). 13 C{ 1 H} NMR (101 MHz, Chloroform-d) δ 170.8, 156.4, 142.1, 141.3, 128.6, 128.5, 127.9, 127.5, 127.2, 69.6, 65.0, 57.9, 50.7, 44.8, 35.8, 30.7, 28.3, 25.1, 23.7. HRMS (ESI) calcd for C 30 H 39 N4O + ([M-I - ]) + = 471.3118, Found 471.3118.

[0104] Example 9: Synthesis of quaternary guanidinium salt IC

[0105] The procedure is similar to that described in Examples 1 and 4-6, with the reaction starting materials replaced according to the differences in the corresponding substituents in the product.

[0106]

[0107] Yellow solid, melting point 143-144 °C; overall yield 55%; [a] 22 D = +69.0 (c = 1.643 g / 100 mL, λ = 589 nm, in CH2Cl2); 1H NMR (400 MHz, Chloroform-d) δ 9.47 (d, J = 9.6 Hz, 1H), 7.62 - 7.60 (m, 2H), 7.54 - 7.52 (m, 2H), 7.33 - 7.30 - 7.28 (m, 4H), 7.22 - 7.12 (m, 6H), 6.28 (d, J = 9.6 Hz, 1H), 5.27 (dd, J = 9.2, 5.2 Hz, 1H), 4.55 (d, J = 13.6 Hz, 1H), 4.25 (d, J = 13.6 Hz, 1H), 3.85 - 2.81 (m, 10H), 2.24 - 1.39 (m, 8H). 13 C{ 1 H} NMR (101 MHz, Chloroform-d) δ 170.2, 157.1, 141.9, 141.5, 133.9, 132.8, 128.6, 128.3, 128.2, 128.1, 127.4, 127.3, 127.1, 127.0, 125.5, 58.5, 57.8, 50.5, 49.9, 33.3, 25.2. HRMS (ESI) calcd for C 32 H 37 N4O + ([M-I - ]) + = 493.2962, Found 493.2962.

[0108] Example 10: Synthesis of quaternary guanidinium salt ID

[0109] The procedure is similar to that described in Examples 1 and 4-6, with the reaction materials replaced according to the difference of the corresponding substituents in the product.

[0110]

[0111] Pale yellow solid, melting point 234-235 °C; total yield 37%; [a] 22 D = +116.8 (c = 0.788 g / 100 mL, λ = 589 nm, in CH2CI2); 1 H NMR (400 MHz, Chloroform-d) δ 9.35 (s, 1H), 7.03 - 6.96 (m, 3H), 5.54 - 5.50 (m, 1H), 3.63 - 3.49 (m, 6H), 3.44 - 3.40 (m, 4H), 3.10 - 3.05 (m, 1H), 2.20 (s, 6H), 2.09 - 2.02 (m, 5H), 1.95 - 1.91 (m, 2H), 1.86 - 1.77 (m, 4H). 13 C{1 H} NMR (101 MHz, Chloroform-d) δ 169.6, 154.7, 135.2, 133.5, 128.1, 127.3, 62.8, 51.8, 50.4, 46.4, 32.6, 25.8, 25.7, 19.0. HRMS (ESI) calcd for C 22 H 33 N4O + ([M-I - ]) + = 369.2649, Found 369.2648.

[0112] Example 11: Synthesis of quaternary guanidine salt IE

[0113] The procedure is similar to that described in Examples 1 and 4-6, with the reaction starting materials replaced according to the differences in the corresponding substituents in the product.

[0114]

[0115] Pale yellow solid, melting point 247-248 °C; total yield 43% yield, [a] 22 D = +99.6 (c = 0.515 g / 100 mL, λ = 589 nm, in CH2CI2). 1 H NMR (400 MHz, Chloroform-d) δ 9.25 (s, 1H), 7.23-7.20 (m, 1H), 7.11-7.09 (m, 2H), 5.64-5.59 (m, 1H), 3.69-3.60 (m, 4H), 3.57-3.50 (m, 2H), 3.47-3.43 (m, 4H), 3.21-3.18 (m, 1H), 3.03-2.96 (m, 2H), 2.11-2.06 (m, 5H), 2.04-1.96 (m, 2H), 1.93-1.80 (m, 4H), 1.20-1.16 (m, 12H). 13 C{ 1 H} NMR (101 MHz, Chloroform-d) δ 170.9, 154.9, 146.1, 130.9, 128.5, 123.5, 62.8, 52.0, 50.6, 32.5, 28.9, 26.0, 25.8. HRMS (ESI) calcd for C 26 H 41 N4O + ([M-I - ]) + = 425.3275, Found 425.3273.

[0116] Example 12: Synthesis of quaternary nitrogen guanidinate salt IF

[0117] The procedure was followed as in Examples 1 and 4-6 with the reaction reagents replaced according to the corresponding substituents in the product.

[0118]

[0119] White solid, overall yield 76%; [a] 23 D = +113.2 (c = 0.865 g / 100 mL, λ = 589 nm, in CH2Cl2); 1 H NMR (400 MHz, Chloroform-d) δ 7.77 (s, 1H), 7.29-7.23 (m, 11H), 6.16 (s, 1H), 4.86 (s, 1H), 3.55-3.26 (m, 10H), 2.70 (s, 1H), 2.05-1.65 m, 11H). 13 C NMR (101 MHz, Chloroform-d) δ 169.8, 154.7, 141.8, 141.1, 128.8, 127.6, 127.5, 127.2, 63.0, 57.5, 51.3, 50.0, 32.0, 25.6. 19 F NMR (377 MHz, Chloroform–d) δ -71.8, -73.7. HRMS (ESI) calcd for C 27 H 35 N4O + ([M – PF6 – ]) + = 431.2805, Found 431.2810.

[0120] Example 13: Synthesis of quaternary nitrogen guanidinate salt IG

[0121] The procedure was followed as in Examples 1 and 4-6 with the reaction reagents replaced according to the corresponding substituents in the product.

[0122]

[0123] White solid, overall yield 76%; [a] 22 D = +110.6 (c = 1.685 g / 100 mL, λ = 589 nm, in CH2Cl2); 1H NMR (400 MHz, Chloroform-d) δ 7.99 (d, J = 9.2 Hz, 1H), 7.38 - 7.36 (m, 2H), 7.31 - 7.27 (m, 6H), 7.24 - 7.19 (m, 2H), 6.14 (d, J = 9.2 Hz, 1H), 4.88 (dd, J = 9.6, 7.2 Hz, 1H), 3.57-3.50 (m, 1H), 3.45-3.38 (m, 5H), 3.26-3.21 (m, 4H), 2.79 - 2.73 (m, 1H), 2.05 - 1.96 (m, 2H), 1.94 - 1.89 (m, 4H), 1.86 - 1.76 (m, 1H), 1.67-1.54 (m, 4H). 13 C NMR (101 MHz, Chloroform-d) δ 169.9, 154.8, 141.9, 141.2, 128.8, 128.8, 127.5, 127.4, 127.4, 127.0, 62.9, 57.4, 51.0, 49.7, 31.9, 25.8, 25.4. 19 F NMR (377 MHz, Chloroform-d) δ -151.8, -151.8. HRMS (ESI) calcd for C 27 H 35 N4O + ([M - BF4 – ]) + = 431.2805, Found 431.2810.

[0124] Example 14: Synthesis of quaternary guanidine salt IH

[0125] The procedure is similar to that described in Examples 1 and 4-6, with the reaction starting materials replaced according to the differences in the corresponding substituents in the product.

[0126]

[0127] White solid, total yield 76%; [a] 22 D = +86.9 (c = 1.155 g / 100 mL, λ = 589 nm, in CH2Cl2); 1H NMR (400 MHz, Chloroform-d) δ 8.48 (d, J = 8.4 Hz, 1H), 7.38 - 7.31 (m, 8H), 7.27 - 7.22 (m, 2H), 6.13 (d, J = 8.4 Hz, 1H), 4.85 (dd, J = 9.6, 7.2 Hz, 1H), 3.58-3.52 (m, 1H), 3.46-3.39 (td, J = 9.9, 6.2 Hz, 4H), 3.33 - 3.29 (m, 1H), 3.24-3.20 (m, 4H), 2.76-2.70 (m, 1H), 2.08 - 1.80 (m, 7H), 1.70-1.58 (m, 4H). 13 C NMR (101 MHz, Chloroform-d) δ 170.1, 154.7, 141.6, 141.2, 128.4, 128.2, 127.5, 127.0, 126.9, 120.5 (d, J C-F = 321.6 Hz), 62.8, 57.5, 51.0, 49.8, 31.8, 25.7, 25.4. 19 F NMR (377 MHz, Chloroform-d) δ -77.9. HRMS (ESI) calcd for C 27 H 35 N4O + ([M - OTf – ]) + = 431.2805, Found 431.2810.

[0128] Example 15: Synthesis of quaternary guanidine salt III

[0129] The procedure is similar to that described in Examples 1 and 4-6, with the reaction starting materials replaced according to the differences in the corresponding substituents in the product.

[0130]

[0131] viscous liquid, 85% overall yield; 1 H NMR (400 MHz, Chloroform-d) δ 8.23 (s, 1H), 7.57 - 7.55 (m, 2H), 7.36 - 7.17 (m, 8H), 6.26 (d, J = 8.8 Hz, 1H), 6.05 (s, 1H), 3.74 - 2.96 (m, 10H), 2.64 - 2.51 (m, 2H), 2.05 - 1.95 (m, 3H), 1.60 - 1.30 (m, 13H), 1.17 - 1.02 (m, 2H), 1.00 - 0.67 (m, 12H). 13C NMR(101MHz,Chloroform-d)171.3,158.0,141.3,141.0,128.2,128.0,126.2,126.1,6 8.6,52.4,49.4,49.3,48.5,33.6,30.2,24.3,20.9,20.7,13.8,13.6.HRMS(ESI)calcd for C 35 H 55 N4O + ([M–I – ]) + =674.3421,Found 674.3420.

[0132] Example 16: Synthesis of Quaternary Nitrogen Guanidine Salt IJ

[0133] For specific procedures, refer to Examples 2 and 4–6. The reaction raw materials are replaced according to the differences in the corresponding substituents in the product.

[0134]

[0135] A viscous liquid, with a total yield of 29%; [α] 22 D =+95.2(c=3.250g / 100mL, λ=589nm, inCH2Cl2); 1 H NMR(400MHz,Chloroform-d)δ4.52(dd,J=9.2,7.6Hz,1H),3.94-3.90(m,1H),3.71(s,3H),3. 56–3.45(m,9H),3.13-3.07(m,1H),2.55-2.49(m,1H),2.08-2.01(m,5H),1.92-1.82(m,5H). 13 C NMR(101MHz,Chloroform-d)δ172.1,154.8,61.2,53.5,53.0,51.1,50.2,46.0,30.8,25.7,25.6,8.8.HRMS(ESI)calcd for C 15 H 26 N3O2 + ([M–Cl – ]) + =280.2020,Found280.2024.

[0136] Example 17: Synthesis of Quaternary Nitrogen Guanidine Salt IK

[0137] General procedure: Refer to examples 1 and 4-6 for the specific procedure. Replace the reaction starting materials according to the difference in the corresponding substituents in the product.

[0138]

[0139] pale yellow solid; melting point: 241-242 °C; overall yield 49%; [a] 21 D = +86.8 (c = 0.630 g / 100 mL, λ = 589 nm, in CH2CI2); 1 H NMR (400 MHz, Chloroform-d) δ 8.63 - 8.54 (m, 1H), 7.08 (s, 2H), 6.64 - 6.63 (m, 1H), 5.29 - 5.28 (m, 1H), 4.13 - 4.03 (m, 2H), 3.74 - 3.57 (m, 10H), 3.36 - 3.31 (m, 2H), 2.91 - 2.80 (m, 1H), 2.78 - 2.68 (m, 1H), 2.14 - 2.05 (m, 5H), 2.01 - 1.88 (m, 7H), 1.81 - 1.74 (m, 2H), 1.69 - 1.67 (m, 1H), 1.56 - 1.53 (m, 1H), 1.44 - 1.42 (m, 1H), 1.26 - 1.20 (m, 18H), 1.10 - 1.05 (m, 2H), 0.92 - 0.84 (m, 1H). 13 C{ 1 H} NMR (101 MHz, Chloroform-d) δ 174.6, 154.0, 152.1, 148.9, 136.5, 123.7, 61.5, 59.9, 54.2, 52.0, 50.7, 34.1, 32.6, 31.4, 31.3, 29.5, 25.9, 25.7, 25.0, 24.6, 24.6, 23.9, 23.7. HRMS (ESI) calcd for C 35 H 58 N5O3S + ([M-I - ]) + = 628.4255, Found 628.4255.

[0140] Example 18: Synthesis of quaternary guanidine salt IL

[0141] General procedure: Refer to examples 1 and 4-6 for the specific procedure. Replace the reaction starting materials according to the difference in the corresponding substituents in the product.

[0142]

[0143] White solid, melting point: 254-255 °C; overall yield 56%; [a] 21 D = +181.2 (c = 0.713 g / 100 mL, λ = 589 nm, in CH2CI2). 1 H NMR (400 MHz, Chloroform-d) δ 9.17 (d, J = 3.6 Hz, 1H), 8.82 - 8.80 (m, 1H), 8.58 (d, J = 2.4 Hz, 1H), 7.86 - 7.78 (m, 1H), 7.60 - 7.55 (m, 3H), 7.22 - 7.12 (m, 3H), 7.07 - 7.03 (m, 1H), 5.49 - 5.36 (m, 1H), 3.64 - 3.50 (m, 5H), 3.33 - 3.28 (m, 5H), 2.88 - 2.81 (m, 1H), 2.14 - 1.99 (m, 7H), 1.80 - 1.73 (m, 4H). 13 C{ 1 H} NMR (101 MHz, Chloroform-d) δ 169.24 - 169.21 (m), 154.97 - 154.90 (m), 153.45 - 153.34 (m), 138.32, 138.26, 130.98 - 130.92 (m), 128.8, 128.08 - 127.96 (m), 127.13 - 127.10 (m), 126.39 - 126.37 (m), 124.64 - 124.53 (m), 124.27 - 124.03 (m), 119.94, 63.91 - 63.84 (m), 51.16 - 51.15 (m), 50.34, 31.94 - 31.87, 25.82, 25.66. HRMS (ESI) calcd for C 27 H 34 35 ClN6O2 + ([M-I - ]) + = 509.2426, Found 509.2428; C 27 H 34 37 ClN6O2 + ([M-I - ]) + = 511.2397, Found 511.2402.

[0144] Example 19: Synthesis of quaternary guanidine salt IM

[0145] General procedure: Refer to examples 1 and 4-6 for specific procedure. Replace the starting materials according to the corresponding substituents in the product.

[0146]

[0147] Light brown solid, melting point: 197-198 °C; total yield 37%; [a] 22 D = +104.3 (c = 0.798 g / 100 mL, λ = 589 nm, in CH2CI2). 1 H NMR (400 MHz, Chloroform-d) δ 8.87 - 8.78 (m, 1H), 7.49 - 7.39 (m, 4H), 7.35 - 7.10 (m, 16H), 6.35 (d, J = 9.0 Hz, 1H), 6.12 - 6.06 (m, 1H), 4.74 - 4.64 (m, 1H), 4.47 - 4.40 (m, 3H), 3.89 - 3.86 (m, 1H), 3.53 - 3.47 (m, 1H), 3.13 (s, 6H), 2.21 - 2.14 (m, 1H). 13 C{ 1 H} NMR (101 MHz, Chloroform-d) δ 168.5, 161.8, 141.4, 141.2, 135.9, 129.6, 129.5, 128.9, 128.8, 127.7, 127.6, 127.5, 127.3, 127.1, 75.7, 62.4, 58.9, 58.3, 51.8, 40.9, 37.4. HRMS (ESI) calcd for C 35 H 36 35 ClN4O + ([M-I - ]) + = 563.2572, Found 563.2570; C 35 H 36 37 ClN4O + ([M-I - ]) + = 565.2543, Found 565.2551.

[0148] Example 20: Synthesis of quaternary guanidine salt IN

[0149] General procedure: Refer to examples 1 and 4-6 for specific procedure. Replace the starting materials according to the corresponding substituents in the product.

[0150]

[0151] White solid, melting point: 231-232 °C; overall yield 36%; [a] 22 D = +117.3 (c = 0.448 g / 100 mL, λ = 589 nm, in CH2Cl2); 1 H NMR (400 MHz, Chloroform-d) δ 8.98 (d, J = 9.2 Hz, 1H), 7.50-7.46 (m, 2H), 7.43-7.39 (m, 2H), 7.35-7.30 (m, 2H), 7.26-7.17 (m, 9H), 7.17-7.13 (m, 4H), 7.10-7.06 (m, 1H), 6.36 (d, J = 9.2 Hz, 1H), 6.03 (t, J = 8.4 Hz, 1H), 5.04 (s, 1H), 4.67 (s, 1H), 4.42 (s, 2H), 4.13 (dd, J = 10.0, 1.6 Hz, 1H), 3.97 (dd, J = 10.0, 2.8 Hz, 1H), 3.07 (s, 6H), 2.04-1.99 (m, 2H). 13 C{ 1 H} NMR (101 MHz, Chloroform-d) δ 169.7, 162.9, 141.5, 141.4, 136.0, 129.6, 129.4, 128.8, 128.8, 127.8, 127.5, 127.4, 127.3, 127.1, 75.7, 70.3, 62.5, 58.2, 40.4, 37.1. HRMS (ESI) calcd for C 35 H 37 N4O2 + ([M-I - ]) + = 545.2911, Found 545.2912.

[0152] Example 21: Synthesis of quaternary guanidine salt IO

[0153] The procedure is similar to that described in Examples 1 and 4-6, with the reaction starting materials replaced according to the corresponding substituents in the product.

[0154]

[0155] Pale yellow solid, melting point: 243-244 °C; overall yield 94%; [a] 22 D = +226.8 (c = 0.585 g / 100 mL, λ = 589 nm, in CH2Cl2); 1H NMR (400 MHz, Chloroform-d) δ 8.92 (d, J = 9.2 Hz, 1H), 7.55 - 7.53 (m, 2H), 7.41 - 7.39 (m, 2H), 7.34 - 7.25 (m, 4H), 7.22 - 7.16 (m, 2H), 6.20 (d, J = 9.2 Hz, 1H), 5.34 - 5.30 (m, 1H), 4.74 (s, 1H), 4.53 (s, 1H), 3.86 - 3.83 (m, 1H), 3.57 - 3.53 (m, 2H), 3.46 - 3.24 (m, 4H), 3.15 - 3.10 (m, 1H), 3.03 - 2.91 (m, 2H), 2.56 - 2.52 (m, 1H), 2.27 - 2.15 (m, 1H), 1.93 - 1.87 (m, 1H), 1.71 - 1.53 (m, 8H), 1.43 - 1.35 (m, 2H), 1.03 - 1.01 (m, 1H). 13 C{ 1 H}NMR (101 MHz, Chloroform-d) δ 170.0, 160.2, 141.9, 141.1, 128.7, 128.7, 128.1, 127.6, 127.3, 69.8, 61.4, 59.1, 58.0, 50.7, 50.2, 49.7, 39.6, 25.7, 25.2, 25.0, 24.8, 23.8, 23.3. HRMS (ESI) calcd for C 29 H 39 N4O2 + ([M-I - ]) + = 475.3068, Found 475.3066.

[0156] Example 22: Synthesis of quaternary guanidine salt IP

[0157] The procedure is similar to that described in Examples 1 and 4-6, with the reaction materials replaced according to the difference of the corresponding substituents in the product.

[0158]

[0159] Pale yellow solid, melting point: 243-244 °C; total yield 33%; [a] 21 D = +140.7 (c = 1.355 g / 100 mL, λ = 589 nm, in CH2Cl2). 1H NMR(400MHz,Chloroform-d)δ8.84(d,J=9.2Hz,1H),7.52–7.50(m,2H),7.40–7.38 (m,2H),7.33–7.26(m,4H),7.22–7.17(m,2H),6.19(d,J=9.2Hz,1H),5.45(dd,J=10 .0,6.8Hz,1H),4.83(s,1H),4.52(s,1H),3.83–3.81(m,1H),3.63–3.61(m,1H),3.4 4–3.35(m,8H),2.82(dd,J=13.2,6.8Hz,1H),1.94–1.87(m,5H),1.67–1.60(m,4H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ170.0,154.6,141.7,141.1,128.6,127.8,127.6,127.3,127.3,70.0,61.2,58.6,57.8,50.1,39.5,25.4.HRMS(ESI)calcd for C 27 H 35 N4O2 + ([MI - ]) + =447.2755,Found 447.2753.

[0160] Example 23: Synthesis of Quaternary Nitrogen Guanidine Salt IQ

[0161] For specific procedures, refer to Examples 1 and 4–6. The reaction raw materials are replaced according to the differences in the corresponding substituents in the product.

[0162]

[0163] White solid, melting point 176–177 °C; overall yield 33%; [α] 22 D =+55.8(c=1.915g / 100mL, λ=589nm, in CH2Cl2); 1H NMR (400 MHz, Chloroform-d) δ 7.74 - 7.72 (m, 8H), 7.56 - 7.55 (m, 4H), 7.38 - 7.28 (m, 6H), 7.20 - 7.13 (m, 4H), 6.17 - 6.12 (m, 2H), 4.60 (dd, J = 10.0, 7.2 Hz, 1H), 4.53 (s, 1H), 3.65 - 3.61 (m, 1H), 3.39 - 3.05 (m, 9H), 2.44 (dd, J = 12.8, 7.2 Hz, 1H), 2.11 - 2.04 (m, 1H), 1.99 - 1.94 (m, 4H), 1.78 - 1.58 (m, 5H). 13 C{ 1 H} NMR (101 MHz, Chloroform-d) δ 168.2, 161.8 (q, 2 J C-F = 50.0 Hz), 154.9, 140.4, 139.8, 134.9, 129.5 - 129.4 (m), 129.2, 128.9-128.8 (m), 128.7, 128.6 - 128.5 (m), 128.4, 128.3, 127.2, 126.9, 124.7 (d, 1 J C-F = 273.6 Hz), 120.6, 117.8 - 117.6 (m), 69.8, 61.1, 58.1, 57.9, 50.0, 39.1, 25.4. 19 F{ 1 H} NMR (377 MHz, Chloroform-d) δ -62.3. HRMS (ESI) calcd for C 27 H 35 N4O2 + ([M-BAr F 4 - ]) + = 447.2755, Found 447.2755.

[0164] Example 24: Synthesis of quaternary guanidinium salt I R

[0165] The procedure is similar to that described in Examples 1 and 4-6, with the reaction materials replaced according to the difference of the corresponding substituents in the product.

[0166]

[0167] Pale yellow solid, total yield 46%; [a] 21 D= + 104.43 (c = 1.015 g / 100 mL, λ = 589 nm, in CH2Cl2). 1 H NMR (400 MHz, Chloroform-d) δ 10.51 (d, J = 8.8 Hz, 1H), 7.36 - 7.30 (m, 4H), 7.19 - 7.05 (m, 6H), 5.14 - 5.10 (m, 1H), 5.04 - 5.00 (m, 1H), 4.36 (d, J = 7.2 Hz, 1H), 3.70 (s, 2H), 3.53 - 3.46 (m, 1H), 3.37 - 3.31 (m, 4H), 3.20 - 3.16 (m, 1H), 3.07 - 3.02 (m, 4H), 2.85 - 2.79 (m, 1H), 2.02 - 1.96 (m, 1H), 1.93 - 1.84 (m, 5H), 1.70 - 1.60 (m, 1H), 1.53 - 1.38 (m, 4H). 13 C NMR (101 MHz, Chloroform-d) δ 169.7, 154.7, 140.5, 140.4, 128.2, 128.1, 127.8, 127.6, 127.3, 127.2, 63.2, 60.4, 60.2, 51.1, 49.7, 31.7, 25.7, 25.2. HRMS (ESI) calcd for C 28 H 38 N5O + ([M-Cl - ]) + = 460.3071, Found 460.3072.

[0168] Example 25: Synthesis of quaternary guanidinium salt IS

[0169] The procedures are similar to those described in Examples 1 and 3-6, with the reaction materials replaced according to the differences in the corresponding substituents in the products.

[0170]

[0171] pale yellow solid, m.p. 167-168 °C; overall yield 39%; [a] 21 D = + 116.9 (c = 0.898 g / 100 mL, λ = 589 nm, in CH2Cl2); 1H NMR(400MHz,Chloroform-d)δ9.24(d,J=9.6Hz,1H),7.58–7.53(m,3H),7.51–7.48(m,4H),7.20–7 .24(m,4H),7.21–7.16(m,2H),6.22(d,J=9.6Hz,1H),5.70(dd,J=9.6,7.2Hz,1H),5.02(d,J=12.0 Hz,1H),4.36(d,J=12.0Hz,1H),4.24–4.22(m,1H),3.71(dd,J=10.4,2.8Hz,1H),3.53–3.46(m,4H ),3.40–3.33(m,2H),3.25–3.20(m,4H),2.02–1.94(m,4H),1.85–1.88(m,1H),1.69–1.56(m,4H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ169.7,154.5,142.0,142.0,141.1,133.2,129.9,128.6,128.6,12 8.6,127.9,127.6,127.3,127.3,122.9,69.3,61.3,58.1,57.1,50.1,35.3,25.4.HRMS(ESI)calcd for C 34 H 39 79 Br2N4O2 + ([MI - ]) + =693.1434, Found 693.1431; C 34 H 39 79 Br 81 BrN4O2 + ([MI - ]) + =695.1414, Found 695.1412; C 34 H 39 81 Br2N4O2 + ([MI - ]) + =697.1393,Found 697.1396.

[0172] Example 26: Synthesis of Quaternary Nitrogen Guanidine Salt IT

[0173] The procedure is similar to that described in Example 1 and 3-6, with the exception that the reaction material is replaced by the corresponding substituent in the product.

[0174]

[0175] Light brown solid, melting point: 141-142 °C; overall yield 38%; [a] 23 D = +136.7 (c = 0.683 g / 100 mL, λ = 589 nm, in CH2CI2). 1 H NMR (400 MHz, Chloroform-d) δ 9.29 - 9.26 (m, 1H), 8.19 - 8.17 (m, 1H), 7.81 - 7.75 (m, 2H), 7.68 - 7.65 (m, 1H), 7.59 - 7.57 (m, 2H), 7.55 - 7.50 (m, 3H), 7.46 - 7.36 (m, 2H), 7.31 - 7.24 (m, 4H), 7.21 - 7.14 (m, 2H), 6.21 (d, J = 9.6 Hz, 1H), 5.77 - 5.71 (m, 1H), 5.46 - 5.42 (m, 1H), 4.88 - 4.82 (m, 1H), 4.24 - 4.22 (m, 1H), 3.62 - 3.58 (m, 1H), 3.47 - 4.38 (m, 5H), 3.24 - 3.21 (m, 1H), 3.15 - 3.11 (m, 4H), 1.93 - 1.81 (m, 5H), 1.63 - 1.53 (m, 4H). 13 C{ 1 H} NMR (101 MHz, Chloroform-d) δ 170.0, 154.4, 142.0, 141.2, 133.8, 133.3, 132.0, 128.8, 128.7, 128.6, 128.5, 128.0, 127.9, 127.7, 127.3, 126.5, 125.8, 125.5, 124.7, 76.3, 76.3, 69.5, 61.4, 58.2, 57.2, 50.0, 35.4, 25.4. HRMS (ESI) calcd for C 38 H 43 N4O2 + ([M-I - ]) + = 587.3381, Found 587.3380.

[0176] Example 27: Synthesis of quaternary guanidine salt IU

[0177] The procedure is similar to that described in Example 1 and 3-6, with the exception that the reaction material is replaced by the corresponding substituent in the product.

[0178]

[0179] Grey solid, melting point: 129-130 °C; overall yield 35%; [a] 23 D = +164.1 (c = 0.315 g / 100 mL, λ = 589 nm, in CH2CI2); 1 H NMR (400 MHz, Chloroform-d) δ 9.23 (d, J = 9.2 Hz, 1H), 7.59 - 7.57 (m, 2H), 7.50 - 7.48 (m, 2H), 7.30 - 7.26 (m, 4H), 7.20 - 7.16 (m, 2H), 6.19 (d, J = 9.2 Hz, 1H), 5.63 (dd, J = 9.4, 7.2 Hz, 1H), 4.14 - 4.12 (m, 1H), 3.91 - 3.85 (m, 1H), 3.70 (dd, J = 10.6, 3.6 Hz, 1H), 3.55 - 3.48 (m, 4H), 3.38 - 3.32 (m, 1H), 3.26 - 3.14 (m, 6H), 2.01 - 1.95 (m, 4H), 1.84 (m, 1H), 1.72 - 1.58 (m, 9H), 1.55 - 1.31 (m, 3H), 1.25 - 1.07 (m, 3H), 0.95 - 0.84 (m, 2H). 13 C{ 1 H} NMR (101 MHz, Chloroform-d) δ 170.2, 154.6, 142.0, 141.1, 128.7, 128.6, 128.1, 127.7, 127.3, 67.4, 61.5, 58.3, 57.3, 50.1, 37.1, 35.5, 34.7, 33.6, 33.5, 26.7, 26.4, 26.4, 25.5. HRMS (ESI) calcd for C 35 H 49 N4O2 + ([M-I - ]) + = 557.3850, Found 557.3851.

[0180] Example 28: Synthesis of quaternary guanidine salt IV

[0181] The procedure is similar to that described in Examples 1 and 3-6, with the reaction materials replaced according to the difference of the corresponding substituents in the product.

[0182]

[0183] White solid, melting point: 291-292 °C; overall yield 18%; [a] 22 D = +122.9 (c = 0.685 g / 100 mL, λ = 589 nm, in CH2CI2). 1 H NMR (400 MHz, Chloroform-d) δ 9.59 (d, J = 9.2 Hz, 1H), 7.70 - 7.61 (m, 6H), 7.53 - 7.51 (m, 2H), 7.45 - 7.35 (m, 6H), 7.30 - 7.26 (m, 4H), 7.20 - 7.15 (m, 2H), 6.17 (d, J = 9.2 Hz, 1H), 5.86 - 5.82 (m, 1H), 4.48 - 4.47 (m, 1H), 3.50 - 3.41 (m, 5H), 3.16 - 3.12 (m, 4H), 2.89 - 2.83 (m, 2H), 2.09 - 1.92 (m, 5H), 1.65 - 1.52 (m, 4H), 1.08 (s, 9H). 13 C{ 1 H} NMR (101 MHz, Chloroform-d) δ 170.2, 154.5, 142.1, 141.2, 136.0, 135.8, 133.8, 132.6, 130.2, 130.0, 128.7, 128.6, 128.1, 127.9, 127.8, 127.2, 77.4, 71.3, 61.7, 58.4, 58.3, 50.0, 39.6, 27.1, 25.4, 19.2. HRMS (ESI) calcd for C 43 H 53 N4O2Si + ([M-I - ]) + = 685.3932, Found 685.3931.

[0184] Example 29: Synthesis of quaternary guanidine salt IW

[0185] The procedure is similar to that described in Examples 1 and 3-6, with the reaction materials replaced according to the difference of the corresponding substituents in the product.

[0186]

[0187] Grey solid, melting point: 126-127 °C. Overall yield 45% yield, [a] 24 D = +142.3 (c = 0.215 g / 100 mL, λ = 589 nm, in CH2CI2). 1H NMR (400 MHz, Chloroform-d) δ 9.22 (d, J = 9.2 Hz, 1H), 7.60 - 7.58 (m, 2H), 7.51 - 7.49 (m, 2H), 7.30 - 7.26 (m, 4H), 7.21 - 7.16 (m, 2H), 6.20 (d, J = 9.2 Hz, 1H), 5.60 - 5.56 (m, 1H), 4.08 - 4.07 (m, 1H), 3.69 (dd, J = 10.4, 3.2 Hz, 1H), 3.56 - 3.49 (m, 5H), 3.25 - 3.11 (m, 6H), 2.81 (d, J = 8.4 Hz, 1H), 2.05 - 1.92 (m, 7H), 1.89 - 1.81 (m, 1H), 1.65 - 1.59 (m, 13H), 1.53 - 1.50 (m, 3H). 13 C{ 1 H} NMR (101 MHz, Chloroform-d) δ 170.2, 154.7, 142.0, 141.1, 128.7, 128.6, 128.1, 127.8, 127.3, 79.7, 61.6, 58.3, 57.0, 50.1, 39.6, 37.3, 35.7, 34.1, 28.4, 25.5. HRMS (ESI) calcd for C 38 H 51 N4O2 + ([M-I - ]) + = 595.4007, Found 595.4006.

[0188] Example 30: Synthesis of quaternary guanidinium salt I X

[0189] The procedures are similar to those described in Examples 1 and 3-6, with the reaction materials replaced according to the differences in the corresponding substituents in the products.

[0190]

[0191] Pale yellow solid, melting point: 129-130 °C. Overall yield 51%; [a] 21 D = +134.4 (c = 0.570 g / 100 mL, λ = 589 nm, in CH2Cl2). 1H NMR (400 MHz, Chloroform-d) δ 9.35 - 9.33 (m, 1H), 7.60 - 7.58 (m, 2H), 7.52 - 7.50 (m, 2H), 7.32 - 7.24 (m, 4H), 7.22 - 7.14 (m, 2H), 7.04 (s, 2H), 6.89 (s, 1H), 6.21 (d, J = 9.2 Hz, 1H), 5.78 - 5.69 (m, 1H), 4.90 - 4.85 (m, 1H), 4.41 - 4.37 (m, 1H), 4.24 - 4.20 (m, 1H), 3.69 - 3.67 (m, 1H), 3.57 - 3.42 (m, 4H), 3.37 - 3.28 (m, 2H), 3.22 - 3.17 (m, 4H), 2.28 (s, 6H), 2.00 - 1.96 (m, 4H), 1.89 - 1.71 (m, 1H), 1.63 - 1.62 (m, 4H). 13 C{ 1 H} NMR (101 MHz, Chloroform-d) δ 170.1, 154.6, 142.1, 141.2, 138.1, 137.5, 129.6, 128.7, 128.6, 128.0, 127.7, 127.3, 126.5, 76.0, 70.9, 61.4, 58.3, 57.3, 50.0, 35.3, 25.4, 21.4, 21.3. HRMS (ESI) calcd for C 36 H 45 N4O2 + ([M-I - ]) + = 565.3537, Found 565.3536.

[0192] Example 31: Synthesis of quaternary guanidine salt IY

[0193] The procedure is similar to that described in Examples 1 and 3-6, with the reaction materials replaced according to the difference of the corresponding substituents in the product.

[0194]

[0195] Grey solid, melting point: 173-174 °C; total yield: 41% yield; [a] 22 D = +132.8 (c = 0.690 g / 100 mL, λ = 589 nm, in CH2CI2). 1H NMR (400 MHz, Chloroform-d) δ 9.28 (d, J = 9.2 Hz, 1H), 7.59 - 7.58 (m, 2H), 7.51 - 7.50 (m, 2H), 7.31 - 7.25 (m, 4H), 7.21 - 7.16 (m, 2H), 6.64 (m, 2H), 6.37 - 6.36 (m, 1H), 6.21 (d, J = 9.2 Hz, 1H), 5.78 - 5.74 (m, 1H), 4.94 - 4.89 (m, 1H), 4.38 - 4.36 (m, 1H), 4.25 - 4.23 (m, 1H), 3.78 (s, 6H), 3.68 (dd, J = 10.4, 3.6 Hz, 1H), 3.54 - 3.45 (m, 4H), 3.35 - 3.31 (m, 2H), 3.23 - 3.28 (m, 4H), 2.00 - 1.96 (m, 4H), 1.87 - 1.74 (m, 1H), 1.69 - 1.56 (m, 4H). 13 C{ 1 H} NMR (101 MHz, Chloroform-d) δ 170.0, 160.9, 154.5, 142.0, 141.2, 140.1, 128.7, 128.6, 128.0, 127.6, 127.3, 106.4, 100.3, 76.2, 70.9, 61.4, 58.2, 57.2, 55.9, 55.8, 50.0, 35.3, 25.4. HRMS (ESI) calcd for C 36 H 45 N4O4 + ([M-I - ]) + = 597.3435, Found 597.3434.

[0196] Example 32: Synthesis of quaternary guanidine salt IZ

[0197] The procedure is similar to that described in Examples 1 and 3-6, with the reaction materials replaced according to the difference of the corresponding substituents in the product.

[0198]

[0199] Pale yellow solid, melting point: 180-181 °C; total yield: 39% yield; [a] 21 D = +128.8 (c = 0.533 g / 100 mL, λ = 589 nm, in CH2Cl2). 1H NMR (400 MHz, Chloroform-d) δ 9.38 (d, J = 9.6 Hz, 1H), 7.59 - 7.57 (m, 2H), 7.51 - 7.49 (m, 2H), 7.34 - 7.33 (m, 1H), 7.32 - 7.26 (m, 4H), 7.25 - 7.12 (m, 4H), 6.21 (d, J = 9.6 Hz, 1H), 5.80 - 5.76 (m, 1H), 4.94 (d, J = 11.2 Hz, 1H), 4.36 (d, J = 11.2 Hz, 1H), 4.25 - 4.23 (m, 1H), 3.70 (dd, J = 10.0, 3.2 Hz, 1H), 3.54 - 3.48 (m, 4H), 3.39 - 3.27 (m, 3H), 3.23 - 3.18 (m, 4H), 2.00 - 1.95 (m, 4H), 1.90 - 1.77 (m, 1H), 1.68 - 1.54 (m, 4H), 1.31 (s, 18H). 13 C{ 1 H} NMR (101 MHz, Chloroform-d) δ 170.1, 154.5, 150.9, 142.0, 141.2, 136.7, 128.7, 128.6, 128.0, 127.7, 127.3, 123.2, 121.9, 76.1, 71.6, 61.5, 58.2, 57.4, 50.0, 48.0, 35.2, 35.0, 31.7, 25.6, 25.4. HRMS (ESI) calcd for C 42 H 57 N4O2 + ([M-I - ]) + = 649.4476, Found 649.4476.

[0200] Example 33: Synthesis of quaternary azaguanidine salt IAA

[0201] The procedure is similar to that described in Examples 1 and 3-6 with the reaction materials replaced by the corresponding substituents in the product.

[0202]

[0203] Yellow solid, melting point: 266-267 °C; overall yield 60%; [a] 23 D = +98.0 (c = 0.545 g / 100 mL, λ = 589 nm, in CH2Cl2); 1H NMR (400 MHz, Chloroform-d) δ 9.26 (d, J = 9.6 Hz, 1H), 7.59 - 7.57 (m, 2H), 7.49 - 7.45 (m, 2H), 7.41 - 7.39 (m, 2H), 7.32 - 7.26 (m, 6H), 7.23 - 7.17 (m, 3H), 6.18 (d, J = 9.6 Hz, 1H), 5.86 (dd, J = 10.0, 7.2 Hz, 1H), 5.36 - 5.35 (m, 3H), 3.80 - 3.77 (m, 3H), 3.51 - 3.44 (m, 4H), 3.23 (dd, J = 11.2, 2.0 Hz, 1H), 3.15 - 3.05 (m, 5H), 2.07 - 1.97 (m, 5H), 1.66 - 1.54 (m, 4H). 13 C{ 1 H} NMR (101 MHz, Chloroform-d) δ 171.4, 169.5, 154.3, 141.9, 141.0, 133.8, 130.0, 128.8, 128.7, 128.1, 127.6, 127.4, 127.1, 72.3, 61.7, 58.3, 55.8, 50.3, 41.6, 36.8, 25.5. HRMS (ESI) calcd for C 35 H 41 N4O3 + ([M-I - ]) + = 565.3173, Found 565.3176.

[0204] Example 34: Synthesis of quaternary guanidinium salt IAB

[0205] The procedures are similar to those described in Examples 1 and 3-6, with the reaction materials replaced by the corresponding substituents in the products.

[0206]

[0207] Yellow solid, melting point: 166-167 °C; overall yield: 76% yield; [a] 21 D = +164.7 (c = 0.338 g / 100 mL, λ = 589 nm, in CH2Cl2). 1H NMR (400 MHz, Chloroform-d) δ 9.31 (d, J = 9.6 Hz, 1H), 7.60 - 7.59 (m, 2H), 7.52 - 7.50 (m, 2H), 7.31 - 7.25 (m, 6H), 7.22 - 7.16 (m, 3H), 7.08 - 7.06 (m, 1H), 6.21 (d, J = 9.6 Hz, 1H), 5.76 (dd, J = 9.2, 7.6 Hz, 1H), 4.94 (d, J = 11.6 Hz, 1H), 4.43 (d, J = 11.6 Hz, 1H), 4.24 - 4.22 (m, 1H), 3.68 (dd, J = 10.4, 3.2 Hz, 1H), 3.53 - 3.47 (m, 4H), 3.38 - 3.30 (m, 2H), 3.22 - 3.18 (m, 4H), 2.33 (s, 3H), 2.00 - 1.96 (m, 4H), 1.89 - 1.81 (m, 1H), 1.69 - 1.61 (m, 5H). 13 C{ 1 H}NMR (101 MHz, Chloroform-d) δ 170.1, 154.6, 142.0, 141.2, 138.2, 137.6, 129.5, 128.7, 128.7, 128.6, 128.5, 128.0, 127.7, 127.3, 125.9, 76.1, 71.0, 61.5, 58.3, 57.3, 50.1, 35.3, 25.4, 21.5. HRMS (ESI) calcd for C 35 H 43 N4O2 + ([M-I - ]) + = 551.3381, Found 551.3381.

[0208] Example 35: Synthesis of quaternary guanidine salt I AC

[0209] The procedures are similar to those described in Examples 1 and 3-6, with the reaction materials replaced according to the difference of the corresponding substituents in the product.

[0210]

[0211] Pale yellow solid, melting point: 137-138 °C; total yield: 49% yield; [a] 21 D = +137.3 (c = 0.758 g / 100 mL, λ = 589 nm, in CH2CI2). 1H NMR (400 MHz, Chloroform-d) δ 9.33 (d, J = 9.6 Hz, 1H), 7.58 - 7.57 (m, 2H), 7.50 - 7.48 (m, 2H), 7.39 - 7.37 (m, 2H), 7.33 - 7.31 (m, 2H), 7.30 - 7.24 (m, 4H), 7.19 - 7.15 (m, 2H), 6.20 (d, J = 9.6 Hz, 1H), 5.73 - 5.68 (m, 1H), 4.94 - 4.90 (m, 1H), 4.40 - 4.38 (m, 1H), 4.23 - 4.20 (m, 1H), 3.69 - 3.66 (m, 1H), 3.52 - 3.44 (m, 4H), 3.33 - 3.30 (m, 2H), 3.20 - 3.15 (m, 4H), 1.96 - 1.95 (m, 4H), 1.86 - 1.81 (m, 1H), 1.67 - 1.54 (m, 4H), 1.27 (s, 9H). 13 C{ 1 H}NMR (101 MHz, Chloroform-d) δ 170.0, 154.5, 150.8, 142.0, 141.2, 134.6, 128.6, 128.6, 128.0, 127.6, 127.3, 125.4, 76.1, 70.7, 61.4, 58.2, 57.3, 50.0, 35.3, 34.6, 31.4, 25.4. HRMS (ESI) calcd for C 38 H 49 N4O2 + ([M-I - ]) + = 593.3850, Found 593.3849.

[0212] Example 36: Synthesis of quaternary guanidinium salt I AD

[0213] The procedure is similar to that described in Examples 1 and 3-6 with the reaction materials replaced by the corresponding substituents in the product.

[0214]

[0215] Light brown solid, melting point: 157-158 °C. Overall yield: 36% yield; [a] 21 D = +144.8 (c = 0.930 g / 100 mL, λ = 589 nm, in CH2Cl2). 1H NMR (400 MHz, Chloroform-d) δ 9.26 (d, J = 9.6 Hz, 1H), 7.60 - 7.50 (m, 10H), 7.42 - 7.39 (m, 2H), 7.33 - 7.24 (m, 5H), 7.20 - 7.15 (m, 2H), 6.23 (d, J = 9.6 Hz, 1H), 5.73 - 5.69 (m, 1H), 5.02 - 4.99 (m, 1H), 4.47 - 4.44 (m, 1H), 4.25 - 4.24 (m, 1H), 3.69 - 3.65 (m, 1H), 3.49 - 3.45 (m, 4H), 3.37 - 3.31 (m, 2H), 3.20 - 3.16 (m, 4H), 1.96 - 1.92 (m, 4H), 1.88 - 1.79 (m, 1H), 1.61 - 1.58 (m, 4H). 13 C{ 1 H} NMR (101 MHz, Chloroform-d) δ 169.9, 154.5, 142.0, 141.1, 140.9, 140.6, 136.7, 129.3, 128.8, 128.6, 128.5, 127.9, 127.6, 127.3, 127.2, 127.2, 127.2, 127.1, 76.3, 70.6, 61.4, 58.1, 57.2, 50.0, 35.3, 25.3. HRMS (ESI) calcd for C 40 H 45 N4O2 + ([M-I - ]) + = 615.3537, Found 615.3538.

[0216] Example 37: Synthesis of quaternary guanidinium salt IA

[0217] The procedure is similar to that described in Examples 1 and 3-6, with the reaction materials replaced according to the difference of the corresponding substituents in the product.

[0218]

[0219] Pale yellow solid, melting point: 237-238 °C; total yield: 49% yield; [a] 21 D = +151.2 (c = 0.955 g / 100 mL, λ = 589 nm, in CH2CI2). 1H NMR (400 MHz, Chloroform-d) δ 9.26 (d, J = 9.6 Hz, 1H), 7.78 - 7.76 (m, 1H), 7.60 - 7.58 (m, 2H), 7.51 - 7.48 (m, 3H), 7.31 - 7.25 (m, 6H), 7.20 - 7.10 (m, 3H), 6.22 (d, J = 9.6 Hz, 1H), 5.73 (dd, J = 9.6, 7.2 Hz, 1H), 5.00 (d, J = 11.2 Hz, 1H), 4.51 (d, J = 11.2 Hz, 1H), 4.33 - 4.32 (m, 1H), 3.75 - 3.71 (m, 1H), 3.53 - 3.47 (m, 4H), 3.39 - 3.28 (m, 2H), 3.21 - 3.17 (m, 3H), 1.97 - 1.88 (m, 5H), 1.85 - 1.79 (m, 1H), 1.69 - 1.54 (m, 4H). 13 C{ 1 H} NMR (101 MHz, Chloroform-d) δ 169.9, 154.4, 142.0, 141.1, 136.9, 132.4, 131.6, 129.5, 128.6, 128.5, 128.0, 127.8, 127.6, 127.3, 127.2, 124.1, 70.6, 61.4, 58.1, 56.9, 50.0, 35.7, 25.4. HRMS (ESI) calcd for C 34 H 40 79 BrN4O2 + ([M-I - ]) + = 615.2329, Found 615.2326; C 34 H 40 81 BrN4O2 + ([M-I - ]) + = 617.2309, Found 617.2304.

[0220] Example 38: Synthesis of quaternary guanidinium salt IAF

[0221] The procedures were followed as in Examples 1 and 3-6 with the reaction materials replaced according to the differences in the corresponding substituents in the products.

[0222]

[0223] Pale yellow solid, melting point: 248-249 °C; overall yield 12%; [a] 23 D= + 113.1 (c = 1.443 g / 100 mL, λ = 589 nm, in CH2Cl2); 1 H NMR (400 MHz, Chloroform-d) δ 9.71 (d, J = 9.6 Hz, 1H), 8.17 (s, 1H), 8.05 (s, 1H), 7.84 - 7.81 (m, 2H), 7.76 - 7.63 (m, 6H), 7.51 - 7.50 (m, 1H), 7.46 - 7.45 (m, 2H), 7.40 - 7.38 (m, 4H), 6.53 (d, J = 9.2 Hz, 1H), 5.71 (dd, J = 10.0, 7.2 Hz, 1H), 4.91 (d, J = 12.0 Hz, 1H), 4.20 (d, J = 12.0 Hz, 1H), 4.06 - 4.04 (m, 1H), 3.61 (dd, J = 10.8, 3.2 Hz, 1H), 3.42 - 3.24 (m, 6H), 3.15 - 3.08 (m, 4H), 1.82 - 1.72 (m, 5H), 1.50 - 1.46 (m, 4H). 13 C{ 1 H} NMR (101 MHz, Chloroform-d) δ 170.0, 154.4, 142.0, 139.2, 138.4, 133.3, 133.3, 133.2, 132.6, 129.8, 128.5, 128.5, 128.3, 128.1, 127.6, 127.6, 126.5, 126.3, 126.2, 126.2, 126.1, 126.0, 125.9, 122.9, 77.4, 69.1, 61.3, 58.3, 57.1, 49.9, 35.1, 25.3. HRMS (ESI) calcd for C 42 H 43 79 Br2N4O2 + ([M-I - ]) + = 793.1747, Found 793.1746; C 42 H 43 79 Br 81 BrN4O2 + ([M-I - ]) + = 795.1727, Found 795.1727; C 42 H 43 81 Br2N4O2 + ([M-I - ]) += 797.1706, Found 797.1716.

[0224] Example 39: Synthesis of quaternary guanidine salt I AG

[0225] The procedure is similar to that described in Examples 1 and 3-6, with the reaction materials replaced according to the differences in the corresponding substituents in the products.

[0226]

[0227] Pale yellow solid, melting point: 191-192 °C; total yield: 25% yield; [a] 23 D = +81.3 (c = 1.723 g / 100 mL, λ = 589 nm, in CH2CI2). 1 H NMR (400 MHz, Chloroform-d) δ 9.07 (d, J = 9.2 Hz, 1H), 7.88 - 7.86 (m, 1H), 7.52 - 7.51 (m, 3H), 7.21 - 7.04 (m, 7H), 6.50 (d, J = 9.2 Hz, 1H), 5.62 - 5.58 (m, 1H), 5.01 (d, J = 11.6 Hz, 1H), 4.27 (d, J = 11.6 Hz, 1H), 4.21 - 4.20 (m, 1H), 3.92 - 3.87 (m, 1H), 3.73 - 3.67 (m, 2H), 3.40 - 3.20 (m, 6H), 3.12 - 2.94 (m, 2H), 2.27 (s, 3H), 2.15 (s, 3H), 2.01 - 1.93 (m, 5H), 1.83 - 1.76 (m, 2H), 1.66 - 1.30 (m, 8H), 1.23 - 1.11 (m, 1H), 0.98 - 0.88 (m, 1H). 13 C{ 1 H} NMR (101 MHz, Chloroform-d) δ 168.8, 160.3, 141.8, 139.3, 138.2, 136.1, 135.3, 133.3, 130.2, 130.1, 128.5, 128.4, 127.4, 127.1, 126.4, 126.2, 122.9, 77.4, 76.5, 69.3, 60.9, 57.8, 52.6, 52.5, 52.3, 52.1, 51.2, 35.3, 29.9, 29.9, 29.6, 29.1, 27.2, 27.0, 26.4, 25.2, 19.5, 19.4. HRMS (ESI) calcd for C 40 H 51 79 Br2N4O2 +([M-I - ]) + = 777.2373, Found 777.2373; C 40 H 51 79 Br 81 BrN4O2 + ([M-I - ]) + = 779.2353, Found 779.2353; C 40 H 51 81 Br2N4O2 + ([M-I - ]) + = 781.2332, Found 781.2339.

[0228] Example 40: Synthesis of amide compound I-7

[0229]

[0230] Amide compound I-5 (1.0 g, 1.7 mmol), K3PO4(4.2 g, 12 mmol), 3,4,5- trifluorobenzoic acid (1.25 g, 7.0 mmol) and Pd(dppf)Cl2(256 mg, 0.35 mmol) were weighed into a 100 mL round bottom flask, a magnetic bar was added and a reflux apparatus was installed, the system was replaced with nitrogen atmosphere, THF / H2O (17 mL:4 mL) was added as solvent, and the reaction was refluxed until the whole system turned black (~5-8 h). After the reaction was completed, THF was removed by rotary evaporation, dichloromethane (20 mL) was added to dissolve, the organic phase was washed with water three times, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and separated by column chromatography (eluent: petroleum ether: ethyl acetate = 1:1-0:1) to obtain the target product I-6 (gray solid, 87% yield).

[0231] Example 41: Synthesis of quaternary nitrogen guanidine salt IAH

[0232] The specific operation refers to Examples 1, 3-6 and 40, and the reaction raw materials are replaced according to the difference of the corresponding substituents in the product.

[0233]

[0234] White solid, melting point: 220-221 °C; total yield 55%; [α] 23 D = +69.1 (c = 0.405 g / 100 mL, λ = 589 nm, in CH2Cl2); 1H NMR (600 MHz, Chloroform-d) δ 9.62 (d, J = 9.0 Hz, 1H), 7.72 - 7.71 (m, 1H), 7.68 - 7.68 (m, 2H), 7.48 - 7.48 (m, 1H), 7.32 - 7.25 (m, 5H), 7.21 - 7.18 (m, 1H), 7.14 - 7.07 (m, 5H), 6.49 (d, J = 9.0 Hz, 1H), 5.81 (dd, J = 9.0, 6.6 Hz, 1H), 5.16 (d, J = 10.8 Hz, 1H), 4.52 (d, J = 10.8 Hz, 1H), 4.35 - 4.34 (m, 1H), 3.76 (dd, J = 10.8, 3.6 Hz, 1H), 3.53 - 3.41 (m, 6H), 3.26 - 3.24 (m, 4H), 2.29 (s, 3H), 2.18 (s, 3H), 2.04 - 2.01 (m, 4H), 1.91 - 1.87 (m, 1H), 1.70 - 1.69 (m, 4H). 13 C{ 1 H} NMR (101 MHz, Chloroform-d) δ 169.2, 154.6, 151.6 (ddd, J C-F = 251.0, 9.6, 3.5 Hz), 140.8, 139.8, 139.2, 138.3, 138.2, 136.8 - 136.6 (m), 136.0, 135.5, 130.4, 130.4, 128.2, 127.9, 127.6, 127.4, 127.3, 126.6, 126.3, 124.8, 111.4 (dd, J C-F = 16.2, 6.0 Hz), 77.4, 70.4, 61.2, 57.3, 51.5, 50.2, 35.6, 25.5, 19.4, 19.4. 19 F{ 1 H} NMR (377 MHz, Chloroform-d) δ -133.7, -133.8, -162.0, -162.0, -162.1. HRMS (ESI) calcd for C 48 H 47 F6N4O2 + ([M-I - ]) + 825.3598, Found 825.3602.

[0235] Example 42: Synthesis of quaternary guanidine salt IA I

[0236] The procedure is similar to that described in Examples 1 and 3-6 with the reaction materials replaced by the corresponding substituents in the product.

[0237]

[0238] White solid, melting point: 167-168 °C; overall yield: 65% yield; [a] 24 D = +113.4 (c = 1.160 g / 100 mL, λ = 589 nm, in CH2CI2). 1 H NMR (400 MHz, Chloroform-d) δ 9.39 (d, J = 9.2 Hz, 1H), 7.53 - 7.52 (m, 1H), 7.50 - 7.49 (m, 2H), 7.38 - 7.36 (m, 1H), 7.32 - 7.22 (m, 4H), 7.19 - 7.15 (m, 1H), 6.92 - 6.88 (m, 2H), 6.19 (d, J = 9.2 Hz, 1H), 5.68 (dd, J = 10.0, 7.2 Hz, 1H), 4.97 (d, J = 12.0 Hz, 1H), 4.35 (d, J = 12.0 Hz, 1H), 4.26 - 4.25 (m, 1H), 3.72 (dd, J = 10.8, 3.2 Hz, 1H), 3.57 - 3.50 (m, 4H), 3.43 - 3.23 (m, 6H), 2.05 - 1.98 (m, 4H), 1.89 - 1.83 (m, 1H), 1.75 - 1.59 (m, 4H). 13 C{ 1 H} NMR (101 MHz, Chloroform-d) δ 170.1, 162.7 (d, 1 J C-F = 247.5 Hz), 154.5, 143.8 (d, 3 J C-F = 7.0 Hz), 142.9 (d, 3 J C-F = 6.9 Hz), 142.0, 133.2, 130.4, 130.3, 129.8, 123.7 (d, 4 J C-F = 2.8 Hz), 123.5 (d, 4 J C-F = 2.9 Hz), 122.9, 114.9 (d, 2 J C-F = 22.1 Hz), 114.8 (d, 2 J C-F = 22.4 Hz), 114.5 (d, 2 J C-F = 20.8 Hz), 114.4 (d, 2 JC-F = 21.0 Hz), 69.3, 61.1, 57.2, 57.1, 50.1, 35.3, 25.4. 19 F{ 1 H} NMR (377 MHz, Chloroform-d) δ -112.3, -112.4. HRMS (ESI) calcd for C 34 H 37 79 Br2F2N4O2 + ([M-I - ]) + = 729.1246, Found 729.1246; C 34 H 37 79 Br 81 BrF2N4O2 + ([M-I - ]) + = 731.1225, Found 731.1228; C 34 H 37 81 Br2F2N4O2 + ([M-I - ]) + = 733.1205, Found 733.1213.

[0239] Example 43: Synthesis of quaternary guanidinium salt IAJ

[0240] The procedures are similar to those described in Examples 1 and 3-6, with the reaction starting materials replaced according to the differences in the corresponding substituents in the products.

[0241]

[0242] Light brown solid, melting point: 153-154 °C; overall yield: 34% yield; [a] 23 D = +76.4 (c = 2.400 g / 100 mL, λ = 589 nm, in CH2CI2). 1H NMR (400 MHz, Chloroform-d) δ 9.11 (d, J = 9.6 Hz, 1H), 7.54 - 7.51 (m, 5H), 7.48 - 7.46 (m, 2H), 7.30 - 7.24 (m, 4H), 6.17 (d, J = 9.6 Hz, 1H), 5.68 (dd, J = 10.0, 6.8 Hz, 1H), 5.01 (d, J = 12.0 Hz, 1H), 4.37 (d, J = 12.0 Hz, 1H), 4.24 - 4.22 (m, 1H), 3.71 (dd, J = 10.6, 3.2 Hz, 1H), 3.51 - 3.40 (m, 5H), 3.34 - 3.22 (m, 5H), 1.96 - 1.91 (m, 4H), 1.88 - 1.79 (m, 1H), 1.69 - 1.50 (m, 4H), 1.24 (s, 9H), 1.21 (s, 9H). 13 C{ 1 H} NMR (101 MHz, Chloroform-d) δ 169.4, 154.5, 149.8, 149.7, 142.0, 139.3, 138.2, 133.2, 129.8, 127.4, 127.1, 125.5, 125.4, 122.8, 69.3, 61.3, 57.4, 57.0, 50.0, 35.2, 34.4, 31.3, 25.3. HRMS (ESI) calcd for C 42 H 55 79 Br2N4O2 + ([M-I - ) + = 805.2686, Found 805.2679; C 42 H 55 79 Br 81 BrN4O2 + ([M-I - ) + = 807.2666, Found 807.2664; C 42 H 55 81 Br2N4O2 + ([M-I - ) + = 809.2645, Found 809.2652.

[0243] Example 44: Synthesis of quaternary azaguanidine salt I AK

[0244] The procedure is similar to that described in Example 1, 3-6 and 40 with the reaction materials replaced by the corresponding substituents in the product.

[0245]

[0246] Grey solid, melting point: 196-197 °C; overall yield: 49% yield; [a] 23 D = +67.0 (c = 2.518 g / 100 mL, λ = 589 nm, in CH2CI2). 1 H NMR (400 MHz, Chloroform-d) δ 8.87 (d, J = 8.8 Hz, 1H), 7.69 - 7.66 (m, 2H), 7.56 (s, 2H), 7.49 - 7.47 (m, 6H), 7.26 - 7.25 (m, 1H), 7.21 - 7.09 (m, 6H), 6.50 (d, J = 8.8 Hz, 1H), 5.72 (t, J = 8.4 Hz, 1H), 5.09 (d, J = 12.4 Hz, 1H), 4.68 (d, J = 12.4 Hz, 1H), 4.34 - 4.33 (m, 1H), 3.71 (dd, J = 10.4, 3.2 Hz, 1H), 3.59 - 3.53 (m, 4H), 3.42 - 3.27 (m, 6H), 2.29 (s, 3H), 2.19 (s, 3H), 2.05 - 2.00 (m, 4H), 1.93 - 1.87 (m, 1H), 1.76 - 1.69 (m, 4H), 1.40 (s, 36H). 13 C{ 1 H} NMR (101 MHz, Chloroform-d) δ 169.4, 154.3, 151.2, 143.3, 140.7, 139.1, 138.5, 138.1, 135.9, 135.4, 130.3, 130.2, 128.1, 127.9, 127.4, 127.2, 126.5, 126.4, 126.2, 126.1, 122.0, 121.6, 77.4, 75.4, 70.6, 61.1, 57.4, 51.4, 50.1, 35.5, 35.0, 31.6, 25.5, 19.3, 19.3. HRMS (ESI) calcd for C 64 H 85 N4O2 + ([M-I - ]) + = 941.6667, Found 941.6667.

[0247] Example 45: Synthesis of quaternary guanidine salt I AL

[0248] The procedure is referred to Examples 1, 3-6 and 40, and the reaction materials are replaced according to the difference of the corresponding substituents in the product.

[0249]

[0250] Grey solid, melting point: 155-156 °C; yield: 32% yield; [a] 24 D = +57.7 (c = 1.343 g / 100 mL, λ = 589 nm, in CH2CI2). 1 H NMR (400 MHz, Chloroform-d) δ 9.01 (d, J = 8.8 Hz, 1H), 8.07 - 8.07 (m, 4H), 7.88 - 7.87 (m, 2H), 7.82 - 7.81 (m, 2H), 7.74 - 7.70 (m, 1H), 7.65 - 7.64 (m, 1H), 7.19 - 7.15 (m, 1H), 6.89 - 6.76 (m, 4H), 6.39 (d, J = 8.8 Hz, 1H), 5.79 (dd, J = 10.0, 7.2 Hz, 1H), 5.32 (d, J = 11.2 Hz, 1H), 4.56 (d, J = 11.2 Hz, 1H), 4.38 - 4.36 (m, 1H), 3.77 (dd, J = 10.4, 3.2 Hz, 1H), 3.58 - 3.51 (m, 5H), 3.39 (dd, J = 10.4, 2.4 Hz, 1H), 3.27 - 3.23 (m, 4H), 2.25 (s, 3H), 2.14 (s, 3H), 2.08 - 2.00 (m, 4H), 1.88 - 1.81 (m, 1H), 1.70 - 1.69 (m, 4H). 13 C{ 1 H} NMR (101 MHz, Chloroform-d) δ 169.2, 162.0 (d, 1 J C-F = 246.2 Hz), 161.9 (d, 1 J C-F = 245.9 Hz), 154.6, 142.7, 140.3, 139.7, 138.3 (d, 3 J C-F = 7.7 Hz), 137.8 (d, 3 J C-F = 7.8 Hz), 134.8 (d, 4 J C-F = 2.7 Hz), 133.8 (d, 4 J C-F = 2.7 Hz), 132.8, 132.3 (d, 2J C-F =33.4Hz), 131.8, 130.0 (d, 3 J C-F =8.6Hz), 129.8(d, 3 J C-F =8.6Hz),128.0,127.7,127.6,127.5,125.6,123.4(d, 1 J C-F =273.7Hz),121.6–121.4(m),119.3,117.1(d, 2 J C-F =21.7Hz), 117.1(d, 2 J C-F =21.2Hz), 113.0(d, 2 J C-F =21.1Hz), 112.7(d, 2 J C-F =20.6Hz),77.4,76.8,70.4,61.1,57.5,50.5,50.1,35.3,25.5,19.4. 19 F{ 1 H}NMR(377MHz,Chloroform-d)δ-62.6,-115.7,-116.1.HRMS(ESI)calcd for C 52 H 47 F 14 N4O2 + ([MI - ]) + =1025.3470,Found1025.3468

[0251] Example 46: Asymmetric alkylation reaction catalyzed by chiral quaternary guanidine salts

[0252]

[0253] Catalyst IAH (9.5 mg, 0.01 mmol), glycine-derived Schiff base (29.5 mg, 0.1 mmol), and cesium carbonate (65.2 mg, 0.2 mmol) were weighed sequentially into a dry reaction tube. Dichloromethane (1.0 mL) and benzyl bromide (34.2 mg, 0.2 mmol) were added. After reacting at 20 °C for two days, column chromatography (eluent: petroleum ether: ethyl acetate = 12:1) was used to separate the product and obtain the corresponding α-alkylated product. The product was a colorless liquid with a yield of 41% and an enantioselectivity of 21%. 1H NMR(400MHz,Chloroform-d)δ7.59–7.56(m,2H),7.40–7.28(m,6H),7.21–7.14(m,3H),7.06–7.04(m,2H) ,6.60(d,J=7.6Hz,1H),4.11(dd,J=9.2,3.6Hz,1H),3.25–3.13(m,2H),1.44(s,9H).HRMS(ESI-FT)calcd for C 26 H 28 NO2 + ([M+H + ])=385.2042,Found 385.2043

[0254] Example 47: Asymmetric α-arylation reaction of benzylene catalyzed by chiral quaternary guanidine salts

[0255]

[0256] In a glove box, various phase transfer catalysts (0.01 mmol), β-ketoamide substrate (32.4 mg, 0.1 mmol), cesium fluoride (45.6 mg, 0.3 mmol), and tetrahydrofuran:toluene (0.5 mL / 0.1 mL) were added sequentially to a reaction tube. Kobayashi's benzyne precursor was added, and the reaction was carried out at 20 °C for three days. Afterward, column chromatography (eluent: petroleum ether: ethyl acetate = 16:1) was used to separate the product, yielding a white solid. 1 H NMR(400MHz,Chloroform-d)δ8.18–8.16(m,1H),7.51–7.47(m,1H),7.37–7.26(m,4H),7.24–7.18(m,3H),6.44(s,1H ),3.04–2.96(m,1H),2.87–2.80(m,1H),2.72–2.60(m,2H),2.05–2.02(m,3H),1.95–1.94(m,6H),1.65–1.63(m,6H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ199.1,168.5,144.6,140.2,134.1,132.7,128.9,128.8, 128.4,127.5,127.4,126.9,63.4,52.2,41.3,36.5,33.8,29.5,26.2.HRMS(ESI-FT)calcd for C 27 H 29 NO2Na +([M+Na + ]) = 422.2091, Found 422.2091

[0257] The technical solutions of the present application are further illustrated by experiments.

[0258] Experimental Example 1: Comparison of catalytic performance of partially quaternary nitrogen guanidine salt catalyst and existing catalyst

[0259] I. Experimental method

[0260] According to the method of Example 47, catalytic reactions were carried out, and the following four compounds were used as catalysts respectively:

[0261]

[0262] The optical purity of the target product was analyzed by high performance liquid chromatography, and the yield and Ee were calculated.

[0263] II. Experimental results

[0264] Table 1

[0265]

[0266]

[0267] The results are shown in Table 1. The most commonly used chiral phase transfer catalysts, such as chiral quaternary ammonium salt catalysts QA1 / QA2 and chiral quaternary phosphonium salt catalysts QP1 / QP2, have very low Ee values in the catalytic asymmetric arylation reaction involving benzyl, indicating that their chiral induction effect is not good. The compounds IP and IAB-IAL provided by the present application both show better chiral induction effect than these existing catalysts. At the same time, when the compounds IP and IAB-IAL of the present application are used as chiral phase transfer catalysts, the catalytic yield reaches 36-89%, meeting the needs of industrial applications.

[0268] The above examples and experimental examples can prove that the present application provides a new type of phase transfer catalyst, which has broad application prospects in the field of asymmetric catalysis.

Claims

1. A compound, characterized in that, The structural formula of the compound is shown in formula Ia or formula Ib: R 1 Selected from: hydrogen, hydroxyl, halogen, substituted or unsubstituted benzyloxy group, substituted or unsubstituted C2 ester group, substituted or unsubstituted C1-C2 alkoxy group, polysubstituted siloxy group, wherein the substituent is selected from C1-C2. 10 Alkyl, C3-C 10 cycloalkyl, C6-C 10 Aryl and halogen-substituted C6-C 10 Aryl, halogen; R 2 Selected from hydrogen; Or, R 1 With R 2 They connect to form phenyl and cyclopentane; R 3 Selected from hydrogen; R 4 Selected from: hydroxyl, substituted or unsubstituted C1-C2 alkylamine, substituted or unsubstituted C1 alkoxy, substituted or unsubstituted aniline, wherein the substituent is selected from halogen, C1-C4 alkyl, C6 ... 10 aryl, methyl-substituted phenyl, amino , ; R a Selected from C1-C6 alkyl, substituted or unsubstituted phenyl groups, wherein the substituents are selected from C1-C4 alkyl or halogens; R 5 R 6 R 7 R 8 They are C1 to C4 alkyl groups, respectively. R 5 With R 6 Connected to form 5-7 member heterocyclic rings; R 7 With R 8 Connected to form 5-7 member heterocyclic rings; X - Selected from: chloride ion, bromide ion, iodide ion, trifluoromethanesulfonate ion, borate ion; n is selected from 0 and 1.

2. A compound, characterized in that, The structural formula of the compound is shown in Formula Ic: Formula Ic in, R b The substituent is independently selected from halogens, C1-C4 alkyl groups, substituted or unsubstituted phenyl groups; wherein the substituent is selected from halogens, fluorinated C1-C4 alkyl groups, C1-C4 alkyl groups, C6-C6 alkyl groups, and C6-C4 alkyl groups. 10 Aryl; R c1 R c2 Each C6 to C6 is independently selected from substituted or unsubstituted C6 to C6. 10 aryl; wherein the substituents are selected from halogens, C1-C4 alkyl groups, C6-C4 alkyl groups, and C6-C4 alkyl groups. 10 Aryl; i and j are independently chosen from 1, 2, or 3; k is chosen from 1 or 2.

3. A compound, characterized in that, The structural formula of the compound is selected from one of the following structures: 。 4. The method for preparing the compound according to claim 1, characterized in that, Includes the following steps: Step 1: React compound I-1 with an alcohol or amine to obtain compound I-2; Step 2: React compound I-2 with trifluoroacetic acid to obtain compound I-3; Step 3: React compound I-3 with imidazoline chloride to obtain compound I-4; Step 4: React compound I-4 with a metal salt to obtain the compound shown in Formula I; The compound structure shown in Formula I is as shown in Formula Ia or Formula Ib, R 3 R 5 R 6 R 7 R 8 As described in claim 1, R 1 Selected from: hydrogen, halogen, substituted or unsubstituted benzyloxy group, substituted or unsubstituted C2 ester group, substituted or unsubstituted C1-C2 alkoxy group, polysubstituted siloxy group, wherein the substituent is selected from C1-C2. 10 Alkyl, C3-C 10 cycloalkyl, C6-C 10 Aryl and halogen-substituted C6-C 10 Aryl, halogen; R 2 Selected from hydrogen; Or, R 1 With R 2 They connect to form phenyl and cyclopentane; R 4 Selected from substituted or unsubstituted C1-C2 alkylamines, substituted or unsubstituted C1 alkoxy groups, and substituted or unsubstituted aniline groups, wherein the substituents are selected from halogens, C1-C4 alkyl groups, and C6-C4 alkyl groups. 10 aryl, methyl-substituted phenyl, amino , ; X - Selected from bromide ions, iodide ions, trifluoromethanesulfonate ions, and borate ions.

5. The preparation method according to claim 4, characterized in that, In step 1, the reaction is carried out in the solvent dichloromethane or tetrahydrofuran, and the alcohol or amine in the reactants is selected from primary amine, secondary amine, primary alcohol, and secondary alcohol. The reaction temperature is 20-50℃ and the reaction time is 4-24 h. And / or, in step 2, the reaction is carried out in the solvent dichloromethane at a temperature of 0–25°C for a time of 1–2 h; And / or, in step 3, the reaction is carried out in the solvent acetonitrile, the reaction is carried out under the action of a base, the base being selected from triethylamine, the reaction temperature is 25-80℃, and the reaction time is 10-24 h; And / or, in step 4, the reaction is carried out in the solvent dichloromethane or tetrahydrofuran at a temperature of 20–35 °C for a time of 4–10 h.

6. Use of the compound according to any one of claims 1-3 as a phase transfer catalyst for catalyzing asymmetric alkylation and / or arylation reactions.

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